Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment
Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment
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DOI：
10.1007/s00213-005-0093-5
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发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
Lucki, I
中科院分区：
文献类型：
--
作者：
Cryan, JF;Page, ME;Lucki, I
基本原理：强迫游泳试验（FST）是用于评估啮齿动物急性或短期治疗后潜在抗抑郁活性的最广泛使用的模型。然而，很少有研究比较了短期和长期抗抑郁治疗对行为的影响，尽管需要长期治疗患者才能产生临床效果。目的：目前的研究探讨了不同类别的抗抑郁药在短期治疗后是否产生不同的行为效应，以及这种效应是否在较长时间给药后发生变化。方法：检查了通过渗透微型泵给予具有不同作用机制的三种不同化学类别的抗抑郁药的短期（3天）和长期（14天）治疗的效果：选择性去甲肾上腺素再摄取抑制剂reboxeratin（10和60 mg kg（-1）天（-1）），选择性5-羟色胺再摄取抑制剂氟西汀（2.5和15 mg kg（-1）天（-1））和单胺氧化酶可逆性抑制剂吗氯贝胺（2.5和15 mg kg（-1）天（-1））。所有的测试进行了15分钟的测试，没有preswim会议，以否定任何混淆方面的诱导processing.Results：大多数抗抑郁药敏感的行为变化，观察在第一个5分钟的测试。低剂量的瑞波西汀在3天后未能改变测试中的行为，但在给药14天后显著降低不动性并增加攀爬行为，而高剂量的瑞波西汀在治疗3天和14天后同样有效。以类似的方式，低剂量的氟西汀在3天后的测试中未能改变行为，但在给药14天后显示出对不动的增强反应和增加的游泳。高剂量氟西汀给药14天后减少不动性的有效性略高于3天。低剂量吗氯贝胺治疗3天后，不动性降低，攀爬行为增加，但治疗14天后，测量到游泳和攀爬行为增加。治疗3天的高剂量吗氯贝胺减少不动和增加游泳，而治疗14天显着增加两个活跃的行为（游泳和攀爬）。结论：三个不同类别的抗抑郁药产生不同的影响，在FST的活跃行为。抗抑郁药的作用在长期给药14天后增强，特别是在低剂量时。这表明FST的修改可用于检查长期给药产生的抗抑郁药的起效时间。
Rationale: The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the test, despite the need to treat patients chronically to produce clinical effects.Objectives: The current studies examined whether antidepressants from different classes produce different behavioral effects following short-term treatment and whether such effects change following administration for a longer duration.Methods: The effects of administering short-term (3 days) and long-term (14 days) treatments of antidepressants from three different chemical classes with distinct mechanisms of action via osmotic minipump were examined: the selective norepinephrine reuptake inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All testing was carried out in a 15-min test with no preswim session in order to negate any confounding aspect of an induction procedure.Results: The majority of antidepressant-sensitive behavioral changes were observed in the first 5 min of the test. The low dose of reboxetine failed to alter behavior in the test after 3 days but significantly decreased immobility and increased climbing behavior following administration for 14 days, whereas the high dose of reboxetine was equally effective following 3 and 14 days of treatment. In a similar fashion, the low dose of fluoxetine failed to alter behavior in the test following 3 days, but showed an augmented response on immobility and increased swimming following administration for 14 days. The high dose of fluoxetine was slightly more effective at reducing immobility following administration for 14 days than 3 days. The low dose of moclobemide decreased immobility and increased climbing behavior following treatment for 3 days, but increases in both swimming and climbing behaviors were measured following treatment for 14 days. Treatment with the high dose of moclobemide for 3 days decreased immobility and increased swimming, whereas treatment for 14 days significantly increased both active behaviors (swimming and climbing).Conclusions: Antidepressants from three different classes produce different effects on active behaviors in the FST. The effects of antidepressants were augmented following chronic administration for 14 days, especially when given at low doses. This suggests that modifications of the FST can be used to examine the onset of action of antidepressant agents produced by long-term administration.